Abstract：
OBJECTIVE: The immune checkpoint inhibitors (ICIs) have been increasingly associated with severe cutaneous adverse reactions (SCARs). These reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP) are uncommon but potentially lethal. Despite the severity of these reactions and growing association with the ICIs, their specific risk and mortality rates have been largely unexplored.
METHODS: A case/non-case analysis was performed using data from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to examine the reporting odds ratios (RORs) for ICI-associated SCARs cases under two conditions: (1) ICIs compared with all drugs in FAERS and (2) ICIs compared with a reference group of pooled anticancer drugs to control for underlying malignancy.
RESULTS: A statistically significant ROR for SJS (ROR: 5.44), TEN (ROR: 5.81) and DRESS (ROR: 1.38) were identified under Condition 1. Under Condition 2, this significance was maintained for SJS (ROR: 7.31), TEN (ROR: 7.40) and DRESS (ROR: 3.90), and mild significance was identified for AGEP (ROR: 1.89). Mortality rates for the ICIs were increased compared with the anticancer medications (28.5% vs. 24.5% for SJS, 55.3% vs. 46% for TEN, 3.0% vs. 2.1% for AGEP and 7.1% vs. 6.1% for DRESS).
CONCLUSIONS: Our results suggest an association between SCARs and the ICIs independent of cancer status.
METHODS: A case/non-case analysis was performed using data from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to examine the reporting odds ratios (RORs) for ICI-associated SCARs cases under two conditions: (1) ICIs compared with all drugs in FAERS and (2) ICIs compared with a reference group of pooled anticancer drugs to control for underlying malignancy.
RESULTS: A statistically significant ROR for SJS (ROR: 5.44), TEN (ROR: 5.81) and DRESS (ROR: 1.38) were identified under Condition 1. Under Condition 2, this significance was maintained for SJS (ROR: 7.31), TEN (ROR: 7.40) and DRESS (ROR: 3.90), and mild significance was identified for AGEP (ROR: 1.89). Mortality rates for the ICIs were increased compared with the anticancer medications (28.5% vs. 24.5% for SJS, 55.3% vs. 46% for TEN, 3.0% vs. 2.1% for AGEP and 7.1% vs. 6.1% for DRESS).
CONCLUSIONS: Our results suggest an association between SCARs and the ICIs independent of cancer status.
摘要：
目的：免疫检查点抑制剂（ICIs）与严重的皮肤不良反应（SCARs）越来越相关。这些反应,包括史蒂文斯-约翰逊综合征（SJS），中毒性表皮坏死松解症（TEN），伴有嗜酸性粒细胞增多和全身症状的药物反应(DRESS)和急性泛发性发疹性脓疱病(AGEP)并不常见,但可能致命.尽管这些反应很严重，而且与ICI的联系也越来越多，它们的特定风险和死亡率在很大程度上尚未被探索。
方法：使用美国食品和药物管理局（FDA）不良事件报告系统（FAERS）的数据进行了病例/非病例分析，以检查以下两种情况下ICI相关SCAR病例的报告优势比（ROR）：（1）ICIs与FAERS中所有药物的比较；（2）ICIs与参考组汇集的抗癌药物以控制潜在恶性肿瘤。
结果：SJS的ROR具有统计学意义（ROR：5.44），在条件1下鉴定出TEN(ROR:5.81)和DRESS(ROR:1.38)。在条件2下，SJS(ROR：7.31)保持了这一显著性，十（ROR：7.40）和连衣裙（ROR：3.90），AGEP有轻度意义（ROR：1.89）。与抗癌药物相比，ICIs的死亡率增加(28.5%vs.SJS的24.5%，55.3%vs.46%为TEN，3.0%与AGEP为2.1%，7.1%与穿着6.1%）。
结论：我们的结果表明SCAR与ICIs之间存在独立于癌症状态的关联。
方法：使用美国食品和药物管理局（FDA）不良事件报告系统（FAERS）的数据进行了病例/非病例分析，以检查以下两种情况下ICI相关SCAR病例的报告优势比（ROR）：（1）ICIs与FAERS中所有药物的比较；（2）ICIs与参考组汇集的抗癌药物以控制潜在恶性肿瘤。
结果：SJS的ROR具有统计学意义（ROR：5.44），在条件1下鉴定出TEN(ROR:5.81)和DRESS(ROR:1.38)。在条件2下，SJS(ROR：7.31)保持了这一显著性，十（ROR：7.40）和连衣裙（ROR：3.90），AGEP有轻度意义（ROR：1.89）。与抗癌药物相比，ICIs的死亡率增加(28.5%vs.SJS的24.5%，55.3%vs.46%为TEN，3.0%与AGEP为2.1%，7.1%与穿着6.1%）。
结论：我们的结果表明SCAR与ICIs之间存在独立于癌症状态的关联。
